NADPH oxidase activity in acute myeloid leukemic cells

Le métabolisme oxydatif joue un rôle important dans l’hématopoïèse normale et leucémique. L’homéostasie des espèces réactives de l’oxygène (ROS) est un élément crucial qui repose sur une balance finement régulée entre leur élimination et leur production. A ce niveau, des études ont montrés une différence entre cellules souches leucémique (CSL) présentant un faible niveau de ROS et cellules différenciées leucoblastiques présentant un plus fort niveau de ROS. Dans cette étude nous avons montré que les NADPH oxydases sont des producteurs majeurs de ROS des cellules de leucémies aiguës myéloïdes. Les cellules leucoblastiques, quelque soit le stade de différenciation présentent une activité NADPH oxydase constitutive qui contribue à leur niveau de ROS élevé et favorise leur prolifération en accélérant le cycle cellulaire. A l’inverse, les analyses réalisées sur des CSL grâce à des modèles murins de leucémies primaires induites par les oncogènes Hoxa9 et Meis1 suggèrent qu’il existerait une plus faible activité oxydase dans les cellules souches leucémiques.Oxydative metabolism play a key role in normal and leukemic hematopoiesis. Reactive oxygen species (ROS) homeostasis is a crucial point which is the result of a finely regulated balance between elimination and production. Recent studies establishe a difference in ROS level between leukemic stem cells (LSC, ROSlow) and differentiated leucoblasts (higher level). In our study we have shown that NADPH oxidases are major ROS producers in acute myeloid leukemic cells. Leukoblasts, wathever their differentition stage, have a constitutive NADPH oxydase activity that contributes to the ROS level and promotes the proliferation by accelerating the cell cycle. Conversly, the analyses of LSCs performed by using murins primary leukemia induced by Hoxa9 and Meis1 oncogens suggest a potential lower NADPH oxidase activity in LSCs

High production of gigantic jets by a thunderstorm over Indian Ocean

Thirteen gigantic jets (GJ) were observed on February 12, 2020, with a sensitive video camera located at Maïdo Observatory, La Réunion Island in Indian Ocean. They were produced within 68 minutes by nearby cells embedded in a convective system almost 500 km from Maïdo. The video imagery combined with the lightning activity from GLD360, the cloud top temperature, the ELF radiations, and the reanalysis of several meteorological parameters allow us to analyze their characteristics and their conditions of production. The altitudes for 12 GJ events are estimated between 85 and 89 km. All jets are of negative polarity and most of them preceded by a positive stroke/pulse in the discharge event. They are produced in sequences of a few minutes, during short pulses of convection within cells in phase of development and associated with dominant positive cloud-to-ground lightning flashes. The most luminous GJ produced the strongest Current Moment (CM) maximum, close to 280 kA km, and the largest Charge Moment Change (CMC). The CMCs associated with the GJ events range from about 1000 C km to close to 5500 C km, especially thanks to the CM during the trailing phase. Several GJ events exhibit a double structure with two jets slightly shifted in space, most of them occurring within the same field of the video imagery. The environment of this exceptional storm in terms of GJ production, exhibits extreme values of various parameters known to be favorable for GJ production, especially related to the warm cloud depth

Complexes de lanthanides à base de dendrimères

The present invention relates to a complex comprising at least one dendrimer and at least one lanthanide, in which the dendrimer comprises a unit of formula (I), wherein: C1 is a group with a valency of 4 of formula >N-CH2-CH2-NN-CH2-CH2-N<; - A1, A2 et A3 sont des groupes de formule -(CH2)2-C(O)-NH-(CH2)2-; ledit motif de formule (I) étant relié de façon covalente à au moins une antenne qui absorbe à une longueur d'onde allant de 500 nm à 900 nm

Characterization of NADPH Oxidase Expression and Activity in Acute Myeloid Leukemia Cell Lines: A Correlation with the Differentiation Status

International audienceIn acute myeloid leukemia (AML), a low level of reactive oxygen species (ROS) is associated with leukemic stem cell (LSC) quiescence, whereas a high level promotes blast proliferation. ROS homeostasis relies on a tightly-regulated balance between the antioxidant and oxidant systems. Among the oxidants, NADPH oxidases (NOX) generate ROS as a physiological function. Although it has been reported in AML initiation and development, the contribution of NOX to the ROS production in AML remains to be clarified. The aim of this study was to investigate the NOX expression and function in AML, and to examine the role of NOX in blast proliferation and differentiation. First, we interrogated the NOX expression in primary cells from public datasets, and investigated their association with prognostic markers. Next, we explored the NOX expression and activity in AML cell lines, and studied the impact of NOX knockdown on cell proliferation and differentiation. We found that NOX2 is ubiquitously expressed in AML blasts, and particularly in cells from the myelomonocytic (M4) and monocytic (M5) stages; however, it is less expressed in LSCs and in relapsed AML. This is consistent with an increased expression throughout normal hematopoietic differentiation, and is reflected in AML cell lines. Nevertheless, no endogenous NOX activity could be detected in the absence of PMA stimulation. Furthermore, CYBB knockdown, although hampering induced NOX2 activity, did not affect the proliferation and differentiation of THP-1 and HL-60 cells. In summary, our data suggest that NOX2 is a marker of AML blast differentiation, while AML cell lines lack any NOX2 endogenous activity